(Hypertension. 1995;25:1260-1265.)
© 1995 American Heart Association, Inc.
Articles |
Opposing Actions of Angiotensin-(1-7) and Angiotensin II in the Brain of Transgenic Hypertensive Rats
Presented in part at the Ninth Scientific Meeting of the American Society of Hypertension, New York, NY, May 11-14, 1994.
From The Hypertension Center, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC (A.M., E.A.T., K.M., C.M.F.); DuPont Merck Pharmaceutical Co, Cardiovascular Disease Research, Wilmington, Del (T.M.R., H.W.); and the Max-Delbrück-Centrum für Molekulare Medizin (MDC), Berlin-Buch, Germany (D.G.).
Abstract Lack of specific antagonists to the amino-terminal heptapeptide angiotensin-(1-7) [Ang-(1-7)] prompted us to evaluate the central effects of delivering a specific affinity-purified Ang-(1-7) antibody on the blood pressure and heart rate of 12-week-old conscious homozygous female rats (n=12) expressing the mouse submandibular Ren-2d gene [(mRen-2d)27] in their genome. Another group of transgenic hypertensive and strain-matched Sprague-Dawley controls were injected with a specific Ang II monoclonal antibody (KAA8). Cerebroventricular administration of the affinity-purified Ang-(1-7) antibody in conscious transgenic hypertensive rats caused significant dose-related elevations in blood pressure associated with tachycardia. The hypertensive response was augmented in transgenic rats studied 7 to 10 days after cessation of lisinopril therapy. Neutralization of Ang II with the Ang II antibody caused a hemodynamic response opposite to that obtained with the Ang-(1-7) antibody. All doses of the Ang II antibody produced hypotension and bradycardia. The magnitude of the depressor response was significantly augmented in transgenic rats weaned off lisinopril therapy. In contrast, central administration of either the Ang-(1-7) or Ang II antibodies had no effect on normotensive rats. Central injections of an affinity-purified IgG fraction were ineffective in both control and transgene-positive rats. These data suggest that in the brain of transgenic hypertensive rats, Ang-(1-7) opposes the action of Ang II on the central mechanism or mechanisms that contribute to the maintenance of this model of hypertension. In addition, these studies showed an important contribution of the brain renin-angiotensin system to the maintenance of this form of monogenetic hypertension.
Key Words: hypertension, genetic • renin-angiotensin system • renin • angiotensins • animals, transgenic • blood pressure
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